First-line Treatment For Patients Research Articles

COVID-19 infection during treatment with pembrolizumab in combination with chemotherapy for the treatment of lung adenocarcinoma

The use of pembrolizumab with chemotherapy in first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) is an opportunity for patients to suppress their disease and increase their chances of life extension. COVID-19 (Coronavirus Disease 2019) vaccination is an opportunity for cancer patients to reduce their risk of disease and have a benign disease course. In this report, we present a benign course of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2 ) infection in 68-year-old patient with metastatic lung adenocarcinoma undergoing chemoimmunotherapy who had previously received full COVID-19 vaccination. The control CT scans performed after 3 months of treatment showed partial regression of the tumor mass. On control tomography after 6 months, an intensification of fibro-consolidative changes and ground glass opacities were described. The lesions were characteristic of a history of SARS-CoV-2 infection. The neoplastic lesions described on tomography showed stabilization. After 9 months, long-term stabilization of the disease was achieved. Patients undergoing immunotherapy or chemoimmunotherapy may be at risk of developing severe COVID-19. Therefore, vaccination against SARS-CoV-2 should be strongly recommended in lung cancer patients undergoing immunotherapy.

Atezolizumab Plus Bevacizumab as First-line Treatment for Patients With Metastatic Nonsquamous Non–Small Cell Lung Cancer With High Tumor Mutation Burden

Antiangiogenic drug combinations with anti-programmed cell death 1 protein and anti-programmed cell death 1 ligand 1 (PD-L1) agents are a novel treatment option for lung cancer. However, survival remains limited, and the activity of these combinations for tumors with high tumor mutation burden (TMB) is unknown. To assess the clinical benefits and safety of atezolizumab plus bevacizumab for patients with high-TMB advanced nonsquamous non-small cell lung cancer (NSCLC). This multicenter, single-arm, open-label, phase 2 nonrandomized controlled trial (Atezolizumab Plus Bevacizumab in First-Line NSCLC Patients [TELMA]) included treatment-naive patients aged 18 years or older with confirmed stage IIIB-IV nonsquamous NSCLC with TMB of 10 or more mutations/megabase and no EGFR, ALK, STK11, MDM2, or ROS1 alterations. From May 2019 through January 2021, patients were assessed at 13 sites in Spain, with follow-up until February 28, 2022. Participants were given atezolizumab, 1200 mg, plus bevacizumab, 15 mg/kg, on day 1 of each 21-day cycle. Treatment was continued until documented disease progression, unacceptable toxic effects, patient withdrawal, investigator decision, or death. The primary end point was 12-month progression-free survival (PFS) rate (according to Response Evaluation Criteria in Solid Tumours, version 1.1 criteria); PFS was defined as the time from enrollment to disease progression or death. Adverse events were monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. A total of 307 patients were assessed for trial eligibility, of whom 266 were ineligible for enrollment. Of the 41 patients enrolled, 3 did not fulfill all inclusion criteria and were excluded. The remaining 38 patients (28 [73.7%] male; mean [SD] age, 63.7 [8.3] years) constituted the per-protocol population. The 12-month PFS rate was 51.3% (95% CI, 34.2%-66.0%), which met the primary end point. The 12-month overall survival (OS) rate was 72.0% (95% CI, 54.1%-83.9%). The median PFS was 13.0 months (95% CI, 7.9-18.0 months), and the median OS was not reached. Of the 38 patients, 16 (42.1%) achieved an objective response and 30 (78.9%) achieved disease control. The median time to response was 2.8 months (IQR, 2.8-3.58 months), with a median duration of response of 11.7 months (range, 3.57-22.4 months; the response was ongoing at cutoff). Of 16 responses, 8 (50.0%) were ongoing. Most adverse events were grade 1 or 2. For atezolizumab, the most common adverse events were fatigue (6 [15.8%]) and pruritus (6 [15.8%]). For bevacizumab, they were hypertension (10 [26.3%]) and proteinuria (4 [10.5%]). Drug discontinuation occurred in 2 patients receiving atezolizumab (5.3%) and 3 patients receiving bevacizumab (7.9%). PD-L1 levels were not associated with response, PFS, or OS. These findings suggest that atezolizumab with bevacizumab is a potential treatment for high-TMB nonsquamous NSCLC. ClinicalTrials.gov Identifier: NCT03836066.

First-line sintilimab plus chemotherapy in locally advanced or metastatic esophageal squamous cell carcinoma: A cost-effectiveness analysis from China.

Objective: The study aimed to assess the cost-effectiveness of sintilimab combined with cisplatin plus paclitaxel versus chemotherapy alone as first-line treatment in patients with advanced or metastatic esophageal squamous cell carcinoma from the Chinese healthcare system. Materials and methods: A partitioned survival model was developed based on the ORIENT-15 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included the health outcomes in life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Result: In overall population, patients given sintilimab plus chemotherapy gained more health benefits (0.90 QALYs vs. 0.61 QALYs), and the cost was more (15,399.21 US$ VS. 7475.58 US$) than that for patients in the chemotherapy group. In the subgroup, patients given sintilimab plus chemotherapy gained more health benefits (0.89 QALYs vs. 0.68 QALYs), and the cost was more (15,656.19 US$ vs. 9,162.77 US$) than that for patients in the chemotherapy group. Compared with chemotherapy, patients receiving sintilimab plus chemotherapy had ICERs of $26,773.68/QALY in the overall population and $30,065.50/QALY in the subgroup, which was above the threshold of WTP. Conclusion: Sintilimab plus chemotherapy was more cost-effective than chemotherapy alone for patients with advanced esophageal cancer from the perspective of the Chinese healthcare system.

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer

SummaryGiven the promising activity and tolerability of FOLFIRINOX as a second-line treatment for advanced biliary tract cancer (BTC), it can be an attractive first-line treatment option as well.This is a single-arm, open-label, multicenter phase II study to evaluate the safety and efficacy of FOLFIRINOX as a first-line treatment for patients with advanced BTC. Primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), tumor response and safety. This study defined primary endpoint might be met when the lower limit value of 80% confidence interval [CI] of the median PFS ≥ 6.0 months.Between June 2016 and March 2020, 35 BTC patients (21 intrahepatic, 10 extrahepatic, 2 gallbladder, 2 ampulla) including 26 unresectable and 9 recurrent disease were enrolled. After a median follow-up of 13.9 months, the median PFS and OS were 7.4 (80% CI, 5.5–7.5) and 14.7 (80% CI, 11.8–15.7) months, respectively. Complete response was achieved in 1 (2.9%) and partial response in 10 (28.6%), giving an objective response rate of 31.4% and disease control rate of 74.3%. Major grade 3–4 adverse events included neutropenia (54.3%), leukopenia (34.4%), febrile neutropenia (17.1%), thrombocytopenia (8.6%), cholangitis (8.6%), anemia, nausea, diarrhea, and peripheral sensory neuropathy (2.9% each).FOLFIRINOX was well tolerable in patients with advanced BTC, however, this study did not meet the primary endpoint to conduct a phase III trial. Thus, further explorations are required to find a subset of patients and/or certain clinical scenario which might be beneficial from FOLFIRINOX.

Trifluridine–tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study

Trifluridine-tipiracil plus bevacizumab has shown efficacy in previous phase 2 studies including patients with unresectable metastatic colorectal cancer. We aimed to investigate first-line trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab in patients with unresectable metastatic colorectal cancer ineligible for intensive treatment. In this open-label, randomised, phase 3 study, we enrolled patients aged 18 years and older with histologically confirmed metastatic colorectal cancer, ineligible for full-dose doublet or triplet chemotherapy and curative resection across 25 countries and regions. Participants were randomly allocated (1:1) to trifluridine-tipiracil plus bevacizumab or capecitabine plus bevacizumab until disease progression or unacceptable toxicity using an interactive web response system, stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), primary tumour location (right vs left colon), and the main reason for not being a candidate for intensive therapy (clinical condition vs non-clinical condition). The primary endpoint was investigator-assessed progression-free survival, defined as the time from randomisation to radiological progression or death from any cause, in the intention-to-treat population. Safety was assessed in all patients having taken at least one dose of the study drug. The trial is ongoing, findings presented here are those of the primary analysis of progression-free survival, conducted after 629 events had occurred. This study is registered with ClinicalTrials.gov, NCT03869892. Between March 21, 2019, and Sept 14, 2020, 856 patients (54% male, 46% female) were randomly assigned to trifluridine-tipiracil plus bevacizumab (n=426) or capecitabine plus bevacizumab (n=430). After a median follow-up of 16·6 months (95% CI 16·5-17·1), the hazard ratio for progression-free survival for trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab was 0·87 (0·75-1·02; p=0·0464; protocol-defined significance level of p=0·021 not met). Investigator-assessed median progression-free survival was 9·4 months (95% CI 9·1-10·9) with trifluridine-tipiracil plus bevacizumab versus 9·3 months (8·9-9·8) with capecitabine plus bevacizumab. The most common grade 3 and higher treatment-emergent adverse events were neutropenia (220 [52%] of 423 patients in the trifluridine-tipiracil plus bevacizumab group vs six [1%] of 427 in the capecitabine plus bevacizumab group), decreased neutrophil count (78 [18%] vs four [<1%]), anaemia (60 [14%] vs 16 [4%]), and hand-foot syndrome (none vs 61 [15%]). Nine deaths (five in the trifluridine-tipiracil plus bevacizumab group and four in the capecitabine plus bevacizumab group) were treatment related. First-line trifluridine-tipiracil plus bevacizumab was not superior to capecitabine plus bevacizumab in this population. As expected, the safety profile differed between the two treatments, but there were no new safety concerns. Trifluridine-tipiracil plus bevacizumab represents a feasible alternative to capecitabine plus bevacizumab in this population. Servier International Research Institute, Suresnes, France.

EE141 Cost-Effectiveness of TP53 and IGHV Biomarker Testing Prior to First-Line Treatment With Novel Agents for Chronic Lymphocytic Leukemia

Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (including del[17p] and mutations) and/or unmutated IGHV (IGHV-U) have inferior survival to standard first-line chemoimmunotherapies and should be considered for novel agents, such as ibrutinib. This study aims to evaluate the cost-effectiveness of predictive biomarker testing for first-line treatment in patients with CLL from an Australian healthcare system perspective.

RWD74 Real-World Effectiveness of CDK 4/6 Inhibitor as First-Line Treatment in Patients With HR+, HER2- Advanced Breast Cancer in South Korea - Focused on Underrepresented Younger and Older Age

RWD74 Real-World Effectiveness of CDK 4/6 Inhibitor as First-Line Treatment in Patients With HR+, HER2- Advanced Breast Cancer in South Korea - Focused on Underrepresented Younger and Older Age

155P BNT113 + pembrolizumab as first-line treatment in patients with unresectable recurrent/metastatic HNSCC: Preliminary safety data from AHEAD-MERIT

BNT113 is an IV administered liposomal ribonucleic acid (RNA-LPX) cancer vaccine encoding the human papillomavirus (HPV)16 oncoproteins E6 and E7. Preclinically, PD-L1 inhibition augments the anti-tumor effect of RNA-LPX-based vaccines, supporting combining BNT113 + pembrolizumab.

CO124 Indirect Comparison of Efficacy and Safety for Aumolertinib vs Osimertinib in Patients With EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

Aumolertinib, an investigational third-generation EGFR inhibitor (EGFRi), has been developed as a first-line treatment for patients with advanced EGFR mutation-positive NSCLC. Aumolertinib and osimertinib, the only approved third-generation EGFRi for this population, have both demonstrated superior safety and efficacy compared to first-generation EGFRis. As no randomized clinical trial (RCT) has directly compared aumolertinib and osimertinib, we conducted an indirect treatment comparison using first-generation EGFRis as the anchor.

65P Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: A large real life worldwide population

Atezolizumab plus bevacizumab and lenvatinib have not been compared in a randomized controlled trial. We conducted a retrospective multi-center study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario.

165P Efficacy and safety of tislelizumab (TIS) plus lenvatinib (LEN) as first-line treatment in patients (pts) with unresectable hepatocellular carcinoma (uHCC): A single-arm, multicenter, phase II trial

The potential advantage of combining anti-PD-1 antibodies with tyrosine kinase inhibitors has been revealed by several trials in advanced HCC. TIS, an anti-PD-1 monoclonal antibody, has shown anti-tumor activity in HCC. LEN is a multikinase inhibitor approved for the first-line treatment of uHCC. This study aims to evaluate the efficacy and safety of TIS plus LEN in pts with uHCC.

Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma

The optimal treatment for and potential benefit populations of synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC) remain unclear. To evaluate outcomes of concurrent chemoradiotherapy (CCRT) and to construct decision tree models for predicting the risk of progression and mortality in patients with SOESCC. This prognostic study included 532 patients with SOESCC who were treated at 2 cancer centers in China from January 2012 to December 2018 and consisted of a development cohort (n = 381) and a validation cohort (n = 151). Data were analyzed from March 2019 to December 2021. All patients received chemotherapy alone or CCRT. The primary end points of the study were progression-free survival (PFS) and overall survival (OS), and the secondary end points were locoregional control and treatment-related toxic effects. Propensity score matching was performed to control potential confounding factors. Cox regression was used to screen important explanatory variables. Decision trees for optimally partitioning patients were established using recursive partitioning analysis and were then subjected to internal and independent external validation. Among the 532 patients (median [range] age, 63 [32-82] years; 367 men [69.0%]), 292 patients received chemotherapy alone and 240 patients underwent CCRT. With a median (IQR) follow-up time of 37.0 (21.6-55.8) months, CCRT was associated with improved objective response rate (139 of 240 [57.9%] vs 123 of 292 [42.1%]; P < .001), median (IQR) PFS (9.7 [8.5-10.9] months vs 7.6 [6.6-8.6] months; P < .001), and median (IQR) OS (18.5 [16.1-20.9] months vs 15.2 [13.6-16.8] months; P < .001) compared with chemotherapy alone. Propensity score matching analysis verified the results. Cox multivariate analysis indicated that treatment modality (CCRT vs chemotherapy alone) was an independent prognostic factor related to PFS (hazard ratio, 0.69; 95% CI, 0.57-0.83; P < .001) and OS (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008). The final decision trees divided patients with SOESCC into low-, intermediate-, and high-risk groups in both the internal and external validations, and the corresponding cumulative risk function curves had significant differences (all P < .001). Time-dependent maximum areas under receiver operating curves of decision trees for progression risk at 3 years and mortality risk at 5 years were 0.820 (95% CI, 0.693-0.948) and 0.894 (95% CI, 0.822-0.966), respectively. Calibration curves also demonstrated that the decision trees had favorable performance of risk stratification. In this study, CCRT vs chemotherapy alone as a first-line treatment for patients with SOESCC had superior survival. Patients with low risk had promising long-term survival based on the current treatment modality. The predictive information of the decision tree could provide accurate decision-making for the management of patients with SOESCC.

EE398 Budget Impact Analysis of Lurasidone in the Treatment of Adult and Adolescent Patients With Schizophrenia in Spain

Although atypical antipsychotics (AA) are the first-line treatments for patients with schizophrenia, for those aged 13-14 years, lurasidone is the only AA licensed. Besides, some AA are related with cardiometabolic events (CME) and lack adherence, generating significant clinical and economic consequences. The aim of this study is to estimate the budget impact (BI) of lurasidone in the management of adult and adolescent (13-17 years) patients with schizophrenia in Spain from a payer's perspective over a 3-years’ time horizon.

EE651 Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy in the First-Line Treatment of Patients With Metastatic Triple-Negative Breast Cancer in Greece

EE651 Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy in the First-Line Treatment of Patients With Metastatic Triple-Negative Breast Cancer in Greece

Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population

Background and aimsAtezolizumab plus bevacizumab and lenvatinib have not been compared in a randomised controlled trial. We conducted a retrospective multi-centre study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario. MethodsClinical features of lenvatinib and atezolizumab plus bevacizumab patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival (OS) was the primary end-point. ResultsThe analysis included 1341 patients who received lenvatinib, and 864 patients who received atezolizumab plus bevacizumab. After IPTW adjustment, atezolizumab plus bevacizumab did not show a survival advantage over lenvatinib HR 0.97 (p = 0.739). OS was prolonged by atezolizumab plus bevacizumab over lenvatinib in viral patients (HR: 0.76; p = 0.024). Conversely, OS was prolonged by lenvatinib in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (HR: 1.88; p = 0.014).In the IPTW-adjusted population, atezolizumab plus bevacizumab provided better safety profile for most of the recorded adverse events. ConclusionOur study did not identify any meaningful difference in OS between atezolizumab plus bevacizumab and lenvatinib. Although some hints are provided suggesting that patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease might benefit more from lenvatinib therapy and patients with viral aetiology more from atezolizumab plus bevacizumab.

Optimal Choice as First-Line Therapy for Patients with Triple-Negative Breast Cancer: A Bayesian Network Meta-Analysis.

To identify the advantageous therapy as the first-line treatment for patients with triple-negative breast cancer (TNBC). Randomized controlled trials were searched for on Medline, Embase, ClinicalTrials.gov, and the Cochrane Library between January 2001 and December 2021. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS) and treatment-related adverse events (TRAEs). A Bayesian framework was applied to facilitate indirect comparisons, of which the outcomes were presented using cumulative ranking curve (SUCRA) values, synthesized hazard ratio, risk ratio, and 95% credible interval. A total of 3140 patients were identified. Pooled results of PFS revealed that chemotherapy plus AKT inhibitors (AKTi) was likely the most effective therapy among enrolled therapies (SUCRA = 91.6%), of which the result remained consistent in comparative analysis for OS. In addition, no significant difference was detected between PD-1/PD-L1 antibodies in patients, whereas the PD-1 inhibitors (PD-1i) regimen was advantageous over PD-L1 inhibitor (PD-L1i) therapy for PD-L1 positive TNBC. Concerning TRAEs, an apparent heterogeneity associated with safety profiles were denoted among enrolled agents. Chemotherapy plus AKTi was the most effective therapy with comparable safety profiles. Chemotherapy plus the anti-PD-1 regimen was advantageous over the combination therapy based on the PD-L1 blockade.

Clinical outcomes of second-generation tyrosine kinase inhibitors versus imatinib in older patients with CML.

Age and comorbidities are important factors to be considered in the selection of tyrosine kinase inhibitors (TKIs) for first-line treatment in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, it is yet unclear whether TKI selection, particularly, imatinib versus second-generation TKIs (2GTKIs), impacts treatment outcomes in the clinical practice. To address this, we compared the clinical outcomes of prospectively registered 452 patients with CML-CP treated with imatinib and 2GTKIs, taking into consideration their age and/or comorbidities. A total of 136 patients (30.1%) were classified into an older cohort (≥65 years) and 316 (69.9%) into a younger cohort (18-64 years). The TKI selection did not vary based on age (70.6% received 2GTKIs in the younger cohort and 66.2% in the older cohort). The median follow-up period was 5.4 years. Treatment responses including the cumulative incidence of deep molecular response (BCR-ABL1 international scale ≤0.0032%) at any time were similar between the two age cohorts regardless of the type of TKI. The 5-year overall survival (OS) in the older cohort was lower than that in the younger cohort (95.9% vs 83.8%; p < 0.0001), whereas the 5-year OS in patients treated with 2GTKIs was not influenced by age factors and comorbidities. Therefore, our results suggest that the selection of 2GTKIs as first-line treatment is an effective option for both younger and older CML-CP patients with or without comorbidities. This trial was registered at UMIN-CTR as 00003581.

Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma

BackgroundIn recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC.MethodsA lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model.ResultsCompared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively.ConclusionSintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.

Phase II Clinical Trial of Camrelizumab Combined with AVD (Epirubicin, Vincristine and Dacarbazine) in the First-Line Treatment for Patients with Advanced Classical Hodgkin's Lymphoma

Background Hodgkin Lymphoma (HL) is a kind of malignant tumor of the lymph system, approximately 95% of which are classical Hodgkin's lymphoma (cHL). ABVD and BEACOPP regimens are commonly used first-line induction treatment regimens for cHL. Sequential radiotherapy for residual lesions or large masses is the current standard treatment after remission. However, disease relapse or drug resistance still occurs in approximately one third of patients, mainly in patients with advanced disease, including Ann Arbor stage III/IV, stage II with B symptoms, and large mediastinal mass or extranodal lesions. Studies have found that the PD-1/PD-L1 pathway plays an important role in the development of cHL disease. Blocking the signaling of the PD-1/PD-L1 pathway may relieve immunosuppression and promote the clearance of RS cells by the immune system. Camrelizumab, a humanized anti-PD-1 IgG4 monoclonal antibody, is independently developed in China. The goal of our trial is to assess the efficacy and safety of Camrelizumab combined with AVD (Epirubicin, Vincristine and Dacarbazine) in the first-line treatment for patients with advanced classical Hodgkin's lymphoma. Methods The patients received 6 cycles of Camrelizumab combined with AVD regimen as first-line therapy. The primary endpoint was objective response rate (ORR), including complete remission (CR) and partial remission (PR), and secondary endpoints were 2-year progression-free survival (PFS), overall survival (OS) and safety. Exploratory endpoints: efficacy and international prognostic score (IPS), hotspot driver gene mutations, characteristic expression (PDL1, BCL2, c-MYC, P53, CD10, BCL6, MUM1/IRF4, and EBER) of tumor cells (RS cells), and correlation of tumor microenvironment and cytokines. Results From September 15, 2019 to June 15, 2022, a total of 20 patients were enrolled, including 4 patients (20%) in stage II, 7 patients (35%) in stage III, and 9 patients (45%) in stage IV; 11 cases (55%) with B symptoms; 1 case (1/16) with IPS score of 0, 5 cases (5/16) with IPS score of 1, 6 cases (6/16) with IPS score of 2, and 2 cases (2/16) with IPS score of 3, and 2 cases (2/16) with IPS score of 4; EBER was positive in 8 cases (40%); lymphoma-related 93 gene detection was performed in 7 cases (35%). At present, 17 patients had completed all the treatments, and the final response of 15 patients had reached CR (88.2%) and 2 patients PR (11.8%). 2-year PFS has not been reached. The combination regimens were well tolerated. Among the 17 patients who had completed all treatments, the common adverse events of treatment were reactive cutaneous capillary endothelial proliferation (RCCEP) in 8 cases (47.1%), gastrointestinal reaction in 6 cases (35.3%), peripheral neuropathy in 4 cases (23.5%), hypothyroidism in 3 cases (17.6%), rash in 2 cases (11.8%), increased AST/ALT levels in 2 cases (11.8%), pneumonitis in 1 case (5.9%), and all of which were grade 1-2. 2 cases of liver function damage was grade 3 (11.8%). Conclusion Camrelizumab combined with AVD has a good effect in the first-line treatment for advanced classical Hodgkin lymphoma, with an objective response rate (ORR) of 100%, and the patients are well tolerated.

Real-World Data Analysis of the Molecular Response Kinetics within the Two First Years of the RELMC-NOVA Study in Newly Diagnosed Spanish CML-CP Patients Treated with Tirosin Kinasa Inhibitors (TKIs) in First Line

Introduction: The RELMC-Nova study analyses first line treatments in patients with chronic myeloid leukemia (CML) in chronic phase (CP) in standard clinical practice in two cohorts, before (retrospective) and after (prospective) the introduction of generic imatinib in 25 hospitals throughout Spain with special emphasis on the molecular kinetics of the initial response (studied as halving time [HT] and with logarithmic reduction [log red] between 2 times). METHODS: 311 patients were registered (171 in the retrospective cohort and 140 in the prospective cohort), all of them treated with TKIs according to standard clinical practice. Molecular Response (MR) was analyzed at 3, 6, 12, 18 and 24 months of treatment in local laboratories according to local clinical practice. HT and log red were calculated between diagnosis and molecular response at 1, 2, 3 and 6 months. RESULTS:Clinical characteristics at diagnosis: total (retrospective (R)/prospective(P)) were the following: Median age 56 years (55/61), Body mass index 24.2 (24.2/24.2), Male-Female 58%-42% (56%-44%/60%-40%), Sokal Index (L-I-H) 44%-43%-13% (50%-37%-13%/37%-51%-12%) and ELTS (L-I-H) 57%-33%-10% (63%-30%-7%/50%-37%-13%). First line TKI: Imatinib (GlivecÒ): 35% (65%/0%), generic Imatinib: 34% (0%/75%), 2nd generation (2nd G) TKIs 30.3% (35%-25%): Nilotinib 20% (22%/17%), Dasatinib 10% (13%/7%), Ponatinib 0.3% (0%/1%). In the retrospective cohort 26.3% of Low o Intermediate Sokal Index patients were treated with 2nd GTKIs versus only 18.2% in the prospective cohort. Overall response rate, total (R/P): See table 1. A statistically significance difference in major molecular response (MMR) between the retrospective and prospective cohorts was only seen at 3 months. Deep molecular response (>MR4), total (R/P): See table 1. No statistically significant differences were observed between cohorts at any time point. Overall response rate, total (Imatinib/2nd GTKIs): See table 1. A statistically significance difference in MMR between imatinib and 2nd GTKIs was only seen at 3 months. Deep molecular response (>MR4), total (Imatinib/2nd GTKIs): See table 1. No statistically significant differences were observed between cohorts at any time point. Only 1 patient (0.32%) showed progression to accelerated phase. Response kinetics: See table 1. Halving time at 3 and 6 months was lower in patients treated with 2nd GTKIs, but without statistical significance. Patients with deep molecular response at 24 months showed a lower HT being statistically significant only at 6 months. Log red: No significant differences were found between patients treated with imatinib and 2nd GTKIs, although results were initially higher in patients treated with 2nd GTKIs. Patients with a deep molecular response at 24 months showed statistically significant differences in log reduction at 3 and 6 months. CONCLUSIONS: 1. Generic imatinib has cornered 1st line treatment increasing from 65% to 75% in the retrospective and prospective cohorts respectively, relegating 2ndGTIKs to high-risk patients. 2. The responses obtained in the first months were higher and faster with the 2nd GTKIs but evened out after 12 months and remained similar at 2 years. 3. Molecular response kinetics (HT or log red) can predict future response and should be assessed in patients with poor early responses. 4. A rapid decline (HR or log red) at the start of treatment guarantees a deep response at 2 years. 5. 2nd GTKIs produce faster molecular response kinetics but final outcomes were similar to that obtained with imatinib. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal